Selective peptide-guided transcytosis enhances extracellular vesicle-mediated siRNA delivery across the blood-brain barrier.

ABSTRACT: Extracellular vesicles (EVs) have clinically emerged as promising biocompatible vesicles for delivering therapeutic siRNAs to the central nervous system. Among targeting strategies, the rabies virus glycoprotein (RVG) peptide is the most commonly used modification on the EV surface to enable efficient systemic delivery of EVs. Although RVG is widely believed to facilitate blood-brain barrier (BBB) through receptor interactions, the underlying mechanism remains indirect and equivocal. Similarly, cell-penetrating peptide (CPP) modifications have been used to enhance BBB transport of various vehicles, such as CPP.16, which improves the brain delivery efficiency of adeno-associated virus 9 capsids. However, whether CPP.16 retains its delivery efficacy when applied to EVs remains unclear, raisi

SUBMITTER: Fang J 

PROVIDER: S-EPMC12753227 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature